17 分子内Double Michael反応を利用するAtisineのエナンチオ選択的全合成(口頭発表の部)

概要

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Atisine (1), isolated from Aconitum heterophyllum, was synthesized via intramolecular double Michael reaction as the key step. The azabicyclo[3.3.1]nonane (5) corresponding to AE part was prepared by double Mannich reaction. The diol (11), derived from 5, was subjected to lipase-catalyzed irreversible transformation to give the (-)-acetate (15) in 100% ee. The absolute configuration of the enantiomer (13) of 15 was determined by X-ray analysis of the perchlorate of (+)-camphorsulfonate (19). The stereoselective introduction of hydrogen atom at the C-9 position of the exoolefin (21) was achieved by hydroboration carried out in the presence of BF_3・OEt_2. The substrate (30) of the intramolecular double Michael reaction was effectively synthesized by further manipulation using Wittig reaction and Birch reduction. The annulation of 30 was performed by action with lithium hexamethyldisilazide and the desired pentacyclic compound (32) was obtained as a single stereoisomer. The unnecessary methoxycarbonyl group of 32 was removed by Barton's free radical decarboxylation procedure. Exchange of the N-protecting group furnished the (-)-acetamide (2) which had been converted to atisine (1) by Pelletier. Thus total synthesis of the naturally occurring form of atisine (1) was achieved in a highly enantioselective manner.
天然有機化合物討論会の論文
1989-09-17